Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LITHIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

Erythrocyte lithium transport changes induced by deoxycorticosterone acetate treatment in pigs.

Ouabain-insensitive lithium efflux from lithium-loaded pig erythrocytes has sodium-dependent and sodium-independent components. Lithium effluxes into sodium (total efflux) and sodium-free (leak) media, sodium-dependent lithium efflux, defined as the difference between total and leak fluxes, and changes in red cell cation and water contents as well as blood pressure were assessed serially for 3 weeks in pigs implanted with Silastic strips impregnated with deoxycorticosterone acetate or with Silastic alone and maintained on a high salt diet (200 mEq/day). Significant differences developed between the groups in blood pressure, red cell sodium content, red cell water content, leak flux, and sodium-dependent lithium efflux (maximal difference: 648 +/- 60 vs 256 +/- 81 mumoles of lithium per liter of cells per hour, deoxycorticosterone acetate vs controls; p less than 0.01). Increased sodium-dependent lithium efflux paralleled a decrease of the diffusional leak component of lithium efflux; total lithium efflux was unchanged. Deoxycorticosterone acetate hypertension in pigs is a useful model in which to study factors modulating erythrocyte cation content and lithium transport in vivo. Changes in lithium transport characterized in red blood cells in this form of experimental hypertension may reflect generalized membrane phenomena.

Animals↗
PubMed2003

Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism.

PURPOSE: To explore whether lithium, a long-standing mood-stabilizing drug, can be used to induce expression of Bcl-2 and support the survival and regeneration of axons of retinal ganglion cells (RGCs). METHODS: Levels of expression of Bcl-2 in the retina were assessed with quantitative reverse transcription-polymerase chain reaction. To determine whether lithium directly supports the survival of and axon-regenerative functions of RGCs, various amounts of lithium were added to cultures of isolated RGCs. Anti-Thy1.2 antibodies-conjugated to magnetic beads were used to isolate the RGCs. In addition, retina-brain slice cocultures were prepared from tissues of Bcl-2-deficient or Bcl-2-transgenic mice and treated with various amounts of lithium. The effects of the expression of Bcl-2 on lithium-mediated functions were then analyzed. RESULTS: Normal mouse retina expressed very low levels of Bcl-2 after birth. Addition of lithium in the culture increased mRNA levels of Bcl-2 in retinas of postnatal mice in a dose-dependent manner. Moreover, lithium promoted not only the survival of RGCs but also the regeneration of their axons. Depleting or forcing the expression of Bcl-2 in RGCs eliminated the effects of lithium. CONCLUSIONS: Lithium supports both the survival and regeneration of RGC axons through a Bcl-2-dependent mechanism. This suggests that lithium may be used to treat glaucoma, optic nerve neuritis, the degeneration of RGCs and their nerve fibers, and other brain and spinal cord disorders involving nerve damage and neuronal cell loss. To achieve full regeneration of the severed optic nerve, it may be essential to combine lithium therapy with other drugs that mediate induction of a permissive environment in the mature central nervous system.

Animals↗
PubMed2006

Lithium leads to an increased FRQ protein stability and to a partial loss of temperature compensation in the Neurospora circadian clock.

In many organisms, the presence of lithium leads to an increase of the circadian period length. In Neurospora crassa, it was earlier found that lithium results in a decrease of overall growth and increased circadian periods. In this article, the authors show that lithium leads to a reduction of FRQ degradation with elevated FRQ levels and to a partial loss of temperature compensation. At a concentration of 13 mM lithium, FRQ degradation is reduced by about 60% while, surprisingly, the activity of the 20S proteasome remains unaffected. Experiments and model calculations have shown that the stability of FRQ is dependent on its phosphorylation state and that increased FRQ protein stabilities lead to increased circadian periods, consistent with the observed increase of the period when lithium is present. Because in Neurospora the proteasome activity is unaffected by lithium concentrations that lead to significant FRQ stabilization, it appears that lithium acts as an inhibitor of kinases that affect phosphorylation of FRQ and other proteins. A competition between Li(+) and Mg(2+) ions for Mg(2+)-binding sites may be a mechanism to how certain kinases are inhibited by Li(+). A possible kinase in this respect is GSK-3, which in other organisms is known to be inhibited by lithium. The partial loss of temperature compensation in the presence of lithium can be understood as an increase in the overall activation energy of FRQ degradation. This increase in activation energy may be related to a reduction in FRQ phosphorylation so that more kinase activity, that is, higher temperature and longer times, is required to achieve the necessary amount of FRQ phosphorylation leading to turnover. Using a modified Goodwin oscillator as a semiquantitative model for the Neurospora clock, the effects of lithium can be described by adding lithium inhibitory terms of FRQ degradation to the model.

Circadian Rhythm↗
PubMed1977

The relationship between extra- and intracellular lithium concentration in human red blood cells: an in vitro study.

Red blood cells (RBC's) from normal volunteers were incubated in vitro at four different extracellular lithium concentrations. Extracellular lithium concentration affected RBC lithium accumulation in several ways. As extracellular lithium concentration increased, the inter-individual variability of RBC lithium accumulation increased. Furthermore, the ratio of RBC lithium concentration to extracellular lithium concentration (lithium ratio) increased in relation to increasing extracellular lithium concentration. A lack of agreement among the authors of recent reports dealing with the significance of the lithium ratio as a psychobiological measure has been noted. It is suggested that this lack of agreement may be due, in part, to the study of patients with differing levels of extracellular lithium.

Cell Membrane Permeability↗
PubMed1989

[Effects of lithium deficient diet on avoidance behavior].

To determine whether lithium deficiency has an effect on lever-press avoidance behavior, low lithium diets were given to mice and the effects of these diets on conditioned lever press avoidance response were compared with that of a commercial diet containing 110 ng Li/g diet. Three low-lithium diets were prepared in this experiment and the lithium contents of the diets were 6.6, 36.6 and 76.6 ng Li/g diet. The mice used in this experiment had been maintained on a practical diet and trained by Sidman's situation previously. After checking that the conditioned response was established, they were divided into four groups. Three groups of mice each were given one of the low lithium diets, indicated above, and these were assigned into the lithium-deficient groups. Some mice were given the practical diet and this group was used as controls. The avoidance behavior was analyzed by the method reported previously by the authors. After changing the diet to a low-lithium one, the avoidance behavior was significantly suppressed in lithium-deficient groups and this appeared to be proportional to the level of lithium deficiency in the diet. Furthermore, this suppression in the avoidance behavior was recovered by lithium supplementation in the same experimental diet. These findings suggest that low-lithium intake may suppress acquired avoidance behavior in mice.

Animals↗
PubMed2001

Mild to severe lithium-induced nephropathy models and urine N-acetyl-beta-D-glucosaminidase in rats.

Long-term treatment with lithium induces functional and/or structural disturbances in the kidneys. However, no procedure has been established for the early diagnosis of lithium intoxication. In this study, we prepared mild to severe lithium-induced nephropathy rat models and examined the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) for the early diagnosis of lithium-induced renal insufficiency. Lithium was administered by repeated intraperitoneal injection (1, 2 and 4 mEq/kg/day for 10 days). We also measured the plasma creatinine and paraaminohippuric acid (PAH) clearance, and observed renal histological changes. Lithium pretreatment elevated the plasma creatinine level and decreased PAH clearance in a dose-dependent manner. The NAG level in the lithium 4 mEq/kg group was very high. The levels in the lithium 1 mEq/kg and 2 mEq/kg groups were almost the same and were higher than the control group. A histological examination of the kidney revealed glomerular congestion and/or atrophy and tubular expansion in all of the groups except the control group. These histological changes were dose-dependent. In conclusion, urine NAG may be useful in the early diagnosis of renal side effects caused by lithium therapy. When the urine NAG level becomes high in a patient taking lithium for bipolar disorder, the physician may need to consider lithium-induced renal insufficiency.

Acetylglucosaminidase↗
PubMed2004

Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium.

Lithium is widely used to treat bipolar disorder, but its mechanism of action in this disorder is unknown. Several molecular targets of lithium have been identified, but these putative targets have not been shown to be responsible for the behavioral effects of lithium in vivo. A robust model for the effects of chronic lithium on behavior in mice would greatly facilitate the characterization of lithium action. We describe behaviors in mice that are robustly affected by chronic lithium. Remarkably, these lithium-sensitive behaviors are also observed in mice lacking one copy of the gene encoding glycogen synthase kinase-3beta (Gsk-3beta), a well established direct target of lithium. In addition, chronic lithium induces molecular changes consistent with inhibition of GSK-3 within regions of the brain that are paralleled in Gsk-3beta+/- heterozygous mice. We also show that lithium therapy activates Wnt signaling in vivo, as measured by increased Wnt-dependent gene expression in the amygdala, hippocampus, and hypothalamus. These observations support a central role for GSK-3beta in mediating behavioral responses to lithium.

Animals↗
PubMed2004

Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases?

The mood stabilizing drug lithium has emerged as a robust neuroprotective agent in preventing apoptosis of neurons. Long-term treatment with lithium effectively protects primary cultures of rat brain neurons from glutamate-induced, NMDA receptor-mediated excitotoxicity. This neuroprotection is accompanied by an inhibition of NMDA-receptor-mediated calcium influx, upregulation of anti-apoptotic Bcl-2, downregulation of pro-apoptotic p53 and Bax, and activation of cell survival factors. Lithium treatment antagonizes glutamate-induced activation of c-Jun-N-terminal kinase (JNK), p38 kinase, and AP-1 binding, which has a major role in cytotoxicity, and suppresses glutamate-induced loss of phosphorylated cAMP responsive element binding protein (CREB). Lithium also induces the expression of brain-derived neurotrophic factor (BDNF) and subsequent activation TrkB, the receptor for BDNF, in cortical neurons. The activation of BDNF/TrkB signaling is essential for the neuroprotective effects of this drug. In addition, lithium stimulates the proliferation of neuroblasts in primary cultures of CNS neurons. Lithium also shows neuroprotective effects in rodent models of diseases. In a rat model of stroke, post-insult treatment with lithium or valproate, another mood stabilizer, at therapeutic doses markedly reduces brain infarction and neurological deficits. This neuroprotection is associated with suppression of caspase-3 activation and induction of chaperone proteins such as heat shock protein 70. In a rat model of Huntington's disease (HD) in which an excitotoxin is unilaterally infused into the striatum, both long- and short-term pretreatment with lithium reduces DNA damage, caspase-3 activation, and loss of striatal neurons. This neuroprotection is associated with upregulation of Bcl-2. Lithium also induces cell proliferation near the injury site with a concomitant loss of proliferating cells in the subventricular zone. Some of these proliferating cells display neuronal or astroglial phenotypes. These results corroborate our findings obtained in primary neuronal cultures. The neuroprotective and neurotrophic actions of lithium have profound clinical implications. In addition to its present use in bipolar patients, lithium could be used to treat acute brain injuries such as stroke and chronic progressive neurodegenerative diseases.

Animals↗
PubMed2003

Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients.

BACKGROUND: Alternatives to lithium for prophylactic treatment of patients with bipolar affective disorders are increasingly being advocated. However, trials comparing lithium with alternatives are scarce and often biased. METHOD: We studied 94 patients with at least 2 episodes of bipolar disorder (DSM-III-R) during the previous 3 years who were in remission at entry into the study. Treatment with lithium or carbamazepine had not exceeded a total of 6 months during their lifetime. Patients were randomly assigned to carbamazepine or lithium at entry into the 2-year double-blind study or during the acute index episode previous to entry into the study. No concurrent antipsychotics or antidepressants were allowed. RESULTS: On lithium treatment, 12/44 patients developed an episode, compared with 21/50 on carbamazepine treatment. Episodes on lithium treatment occurred almost exclusively during the first 3 months of the trial. Carbamazepine carried a constant risk of an episode of about 40% per year. Efficacy of lithium was superior to that of carbamazepine in patients with a (hypo)manic index episode that had not been treated with study drug during the index episode (p <.01) and also in patients with prior hypomanic but no manic episodes (p <.05). The proportion of patients who dropped out was slightly higher among those taking lithium (16/44) compared with those taking carbamazepine (13/50), resulting in 16/44 patients (36%) on lithium treatment completing the 2 years with no episode, compared with 16/50 (32%) on carbamazepine treatment. CONCLUSION: Lithium appears to be superior in prophylactic efficacy to carbamazepine in bipolar patients not previously treated with mood stabilizers. Our results should reinforce efforts to put and maintain such patients on treatment with lithium.

Adult↗
PubMed1999

Lithium therapy and suicide risk.

BACKGROUND: Studies from the early 90s have suggested that patients selected for and compliant with treatment at specialized lithium clinics have lower-than-expected suicide rates. The present study examines whether such findings can be replicated under less select treatment conditions. METHOD: All 362 patients in Göteborg, Sweden, with DSM-III-R mood or schizoaffective disorders, hospitalized at least once during an 8-year period and treated with lithium for a minimum of 1 year, were followed. The study included 3911 patient-years on lithium and, because of permanent or temporary discontinuation, 1274 patient-years off lithium. RESULTS: The risk of suicide was significantly increased on (standard mortality ratio [SMR] = 6.1) as well as off lithium (SMR = 29.0), but the relative risk of suicide was 4.8 times higher during periods off lithium (p < .02; 95% confidence limits 1.1 to 12.6). Ongoing lithium treatment was associated with a 77% reduction in the risk of suicide, whereas alcohol or drug abuse was associated with a 284% increased risk. CONCLUSION: The findings suggest that ongoing lithium treatment is associated with a lower suicide risk. Whether this is due to lithium's mood-stabilizing properties, to lower suicide risk per se in the patients who remain in treatment, or to a specific antisuicidal effect of the lithium ion cannot be determined since patients were not randomized to discontinue treatment. This methodological shortcoming is shared with every study in the field. All results regarding the influence of lithium on suicide rates must therefore be interpreted with extreme caution.

Cause of Death↗
PubMed2000

Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness.

Although mood disorders have traditionally been conceptualized as "neurochemical disorders," considerable literature from a variety of sources demonstrates significant reductions in regional central nervous system (CNS) volume and cell numbers (both neurons and glia) in persons with mood disorders. It is noteworthy that recent advances in cellular and molecular biology have resulted in the identification of 2 novel, hitherto completely unexpected targets of lithium's actions, discoveries that may have a major impact on the future use of this unique cation in biology and medicine. Chronic lithium treatment has been demonstrated to markedly increase the levels of the major neuroprotective protein bc1-2 in rat frontal cortex, hippocampus, and striatum. Similar lithium-induced increases in bc1-2 are also observed in cells of human neuronal origin and are observed in rat frontal cortex at lithium levels as low as approximately 0.3 mM. Bc1-2 is widely regarded as a major neuroprotective protein, and genetic strategies that increase bc1-2 levels have demonstrated not only robust protection of neurons against diverse insults, but have also demonstrated an increase in the regeneration of mammalian CNS axons. Lithium has also been demonstrated to inhibit glycogen synthase kinase 3beta (GSK-3beta), an enzyme known to regulate the levels of phosphorylated tau and beta-catenin (both of which may play a role in the neurodegeneration observed in certain forms of Alzheimer's disease). Consistent with the increases in bc1-2 levels and inhibition of GSK-3beta, lithium has been demonstrated to exert robust protective effects against diverse insults both in vitro and in vivo. These findings suggest that lithium may exert some of its long-term beneficial effects in the treatment of mood disorders via underappreciated neurotrophic and neuroprotective effects. To date, lithium remains the only medication demonstrated to markedly increase bc1-2 levels in several brain areas; in the absence of other adequate treatments, an investigation of the potential efficacy of lithium in the long-term treatment of several neurodegenerative disorders is warranted. Additionally, we suggest that a reconceptualization of the use of lithium in mood disorders may be warranted-namely, that the use of lithium as a neurotrophic/neuroprotective agent should be considered in the long-term treatment of mood disorders, irrespective of the "primary" treatment modality being used for the condition.

Animals↗
PubMed2001

[Behavioral and neurochemical study on the mechanism of the anxiolytic effect of a selective serotonin reuptake inhibitor, a selective serotonin1A agonist and lithium carbonate].

The authors investigated the effects of citalopram [selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist) following treatment with subchronic lithium (p.o., 1 week) on the expression of conditioned freezing, an index of anxiety, and on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). In conditioned fear stress experiments, acute administration of citalopram (s.c.) reduced freezing significantly at a high dose (30 mg/kg), while showing no effect at lower doses (3 and 10 mg/kg). Acute administration of MKC-242 (s.c.; 0.1-10 mg/kg) dose-dependently reduced freezing. Subchronic lithium treatment (1 week; 0.05 or 0.2% lithium carbonate in diet; p.o.) showed no effect on freezing behavior. Acute treatment with both citalopram (3 and 30 mg/kg) and MKC-242 (1 mg/kg) after subchronic treatment with high, but not low, concentrations of lithium (1 week) reduced freezing markedly and significantly, as compared with either drug alone. In brain microdialysis experiments, acute treatment with citalopram showed significant increases in the extracellular 5-HT concentrations in a dose-dependent manner. Subchronic lithium group showed significantly higher basal levels of extracellular 5-HT, compared with normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Subchronic lithium did not cause decreases in extracellular 5-HT after presynaptic stimulation of 5-HT1A receptors by MKC-242. These results suggest that subchronic lithium treatment enhanced the anxiolytic-like effects of these serotonergic drugs by facilitating central 5-HT neurotransmission at clinically therapeutic plasma lithium levels. It is hypothesized that subchronic lithium treatment gives an additive effect to the treatment with citalopram (3 and 30 mg/kg) by increasing the extracellular 5-HT concentrations in the mPFC, and that subchronic lithium treatment enhances the anxiolytic effect of MKC-242 by increasing sensitivity of postsynaptic 5-HT1A receptors.

Animals↗
PubMedDate not supplied

Is lithium still worth using? An update of selected recent research.

The treatment of bipolar disorder has seen greater innovation in the past decade than at any other time since the introduction of lithium and the neuroleptics a half-century ago. The place of lithium in contemporary psychiatric therapeutics has become controversial, calling for the present overview of research findings pertaining to its use in treating patients with bipolar disorder. Lithium, by itself, typically is inadequate for rapid control of acute mania; antipsychotics, divalproex, or potent sedatives are commonly used, with or without lithium, for this purpose. The special usefulness of lithium lies in long-term prevention of recurrences of mania and bipolar depression and in reducing risk of suicidal behavior. Lithium also may be beneficial in recurrent unipolar depression and is an effective adjunct for treatment-resistant depression. Expectations that prolonged untreated bipolar illness, multiple episodes, rapid cycling, or retreatment following discontinuation might routinely lead to lithium nonresponsiveness, and the belief that lithium is too toxic for use during pregnancy, have not been borne out by research. Lithium retains a substantial share of prescriptions for bipolar disorder and is inexpensive. No other treatment has performed as well as lithium in as many aspects of long-term care of bipolar disorder patients, and despite some risks and limitations, lithium remains the standard against which all proposed alternatives are compared.

Antimanic Agents↗
PubMedDate not supplied

[Long-term lithium prophylaxis in the bipolar affective disorder].

The purpose of the study was to evaluate the efficacy of lithium prophylaxis in patients with bipolar affective disorder and to determine clinical differences between lithium responders and non-responders. Clinical and demographic data of 103 patients treated with lithium for at least 10 years were analysed. 24 patients had no episodes on lithium (excellent responders--ER), in 48--at least 50% reduction of episode index (number of episodes/year) was observed, and the remaining 31 did not benefit from lithium treatment. Duration of illness before lithium introduction was significantly longer in lithium non-responders. Lithium responders had significantly higher episode index before lithium. Percentage of excellent responders diminished during treatment. The trend toward higher lithium plasma level in excellent responders was observed. Non-responders had significantly more depressions during first year of lithium prophylaxis. Depressive episodes during first year of treatment may be a predictor of non-response.

Adult↗
PubMed1992

Amiloride-sensitive lithium reabsorption in rats: a micropuncture study.

It has been suggested that in sodium-restricted rats lithium is being reabsorbed in the collecting tubule, and that such reabsorption can be prevented by amiloride. We studied these options in rats by means of cortical micropuncture. Indeed, an important fraction of the filtered lithium (10.5%) was reabsorbed beyond the early distal tubule in sodium-restricted rats. Amiloride infusion abolished this reabsorption. The dosage used did not affect the reabsorption of water, sodium and lithium in the proximal tubule, and also did not change the reabsorption of water and sodium in the loop segment. However, the reabsorption of lithium in this segment tended to be higher during amiloride (P = .06), and the delivery of lithium to the early distal puncture site was significantly less (26.1 +/- 1.2%) than in the control rats (31.4 +/- 1.8%, P < .05). The reason for this apparent increase in lithium reabsorption in the loop segment is not clear. Interestingly, amiloride increased urine flow and decreased urine osmolality. The mechanism underlying this effect needs further exploration. We conclude that in sodium-restricted rats lithium reabsorption beyond the early distal tubule level occurs. Lithium clearance data therefore underestimate end-proximal delivery under these conditions. Lithium reabsorption beyond the early distal tubule can be prevented by amiloride treatment. However, because amiloride may stimulate lithium reabsorption further upstream, lithium clearance data obtained during amiloride infusion may still underestimate end-proximal delivery of water and sodium.

Absorption↗
PubMed2006

[Treatment of acute lithium intoxication with high-flux haemodialysis membranes].

Lithium carbonate is commonly prescribed for the treatment of bipolar (manic-depressive) disorders. However, because of its narrow therapeutic index an excessive elevation of serum lithium concentration, either during chronic maintenance therapy or after an acute overdose, can result in serious toxicity. In addition to supportive care, the established treatment of severe lithium toxicity is haemodialysis. Conventional haemodialysis can reduce serum lithium rapidly, but post-dialysis rebound elevations with recurrent toxicity have been documented in old publications. High-flux membranes should be capable of removing more lithium per hour of haemodialysis, but published values are not available. We report here three patients with acute lithium intoxication who were treated successfully with bicarbonate and high-flux haemodialysis membranes. Our patients presented with a severe degree of intoxication, based on the amount of drug ingested, the initial serum lithium level, the severity of neurologic symptoms and systemic manifestations. Two patients developed acute renal failure probably as a result of volume depletion since it was rapidly reversible by haemodialysis and infusion therapy. In addition, consecutive haemodialysis sessions and improvement of renal function allowed a rapid decrease in serum lithium levels without haemodynamic instability or rebound elevations in lithium concentration. The effectiveness of the procedure in these cases can be attributed to the use of bicarbonate dialysate and high-efficiency dialysers. This is the first report describing the effect of high-efficiency dialysers on lithium pharmacokinetic. Using this technique the elimination rate of lithium was found to be greater than previously reported with haemodialysis.

Acute Disease↗
PubMed1978

Lithium intoxication. (Report of 23 cases and review of 100 cases from the literature).

Twenty-three patients were studied, 21 of whom developed intoxication during maintenance therapy with a lithium dosage which had been unchanged for months to years. Toxic effects on brain, heart and kidneys were found and the severity of lithium intoxication seemed to depend on at least three factors: the height of the serum lithium concentration (SLi), the duration of lithium intoxication and individual tolerance. Disorders of water and electrolyte metabolism preceded lithium intoxication in the majority of the patients. Water loss due to impaired renal concentrating ability seemed to be a major predisposing factor. Renal insufficiency was apparent in 17 of the patients on admission and five of these did not regain normal renal function. In seven patients, renal biopsy showed abnormalities which suggest that a chronic nephropathy, possibly caused by lithium, might be another predisposing factor. Treatment with sodium chloride infusion had no specific effect on lithium excretion and led to hypernatraemia in some patients and is therefore not recommended. Hemodialysis is the most effective method available for removing the lithium ion from intoxicated patients. Hemodialysis should be carried out long enough to secure a SLi of less than 1 mmol/l after redistribution of lithium in the body. Treatment by peritoneal dialysis is appropriate only if hemodialysis facilities are unavailable. Lithium intoxication is a serious condition. Of the 23 patients reported, two died and two developed persisting neurological sequelae. The best way to prevent lithium intoxication is to control the serum concentration and to assess renal function and renal concentrating ability regularly during therapy.

Acute Kidney Injury↗
PubMed1987

Influence of diuretics on renal lithium excretion and tissue distribution of some cations in saline loaded young and adult rats.

In 5- and 105-day-old rats the effect of acetazolamide, cyclopenthiazide, and/or a saline load on renal lithium excretion as well as on lithium, sodium and potassium concentrations in serum and in various tissues (kidney, muscle, intestine, liver, brain) was investigated during the first 3 h after ip. administration of lithium. The administration of acetazolamide or saline led to a significant increase in renal lithium elimination in animals of both age groups, which could be stimulated additionally, when both substances were given simultaneously. In principle, increased renal lithium excretion is paralleled by enhanced sodium elimination. There was evidence for an inhibition of renal tubular lithium reabsorption and besides, extrarenal changes were observed in the lithium, sodium, and potassium distribution, which have consequences for lithium elimination as well. Lithium is accumulated to a different extent in each of the tissues investigated. Furthermore, tissue accumulation and efflux rate of lithium strongly depend on age. The influences of the diuretics and/or saline administration on possible mechanisms of renal and extrarenal lithium movements are discussed.

Acetazolamide↗